Most patients having formed a kidney stone composed of calcium oxalate alone or with apatite demonstrate normal serum Ca levels, hypercalciuria, imparied absolute renal Ca conservation, augmented intestinal Ca absorption, accelerated skeletal Ca turnover and Ca crystalluria when compared to subjects without a personal or family history of stones. In addition, stone formers exhibit hypophosphatemia, impaired maximal renal PO4 conservation and elevated plasma 1,25-(OH)2-D concentrations. Serum iPTH levels may be normal, low or in the upper reaches of the normal range. The hypercalciuria in stone formers has been attributed to a renal Ca leak with secondary hyperparathyroidism, relative phosphate depletion and activation of renal 1,25-(OH)2-D synthesis. Alternatively a primary defect in phosphate homeostasis might directly increase 1,25-(OH)2-D synthesis and thus produce increased intestinal Ca absorption and skeletal Ca turnover. Most stone formers are men (M:F equals 3:1) whereas normal men appear to be resistent to dietary PO4 deprivation. We propose to continue to evaluate the control of serum 1,25-(OH)2-D levels and H3, 1,25-(OH)2-D turnover in normal subjects deprived and loaded with PO4 or Ca and in stone formers before and after therapy with PO4 or a thiazide diuretic. BIBLIOGRAPHIC REFERENCES: Carothers, J.E., N.M. Kurtz and J. Lemann, Jr. Error introduced by specimen handling before determination of inorganic phosphate concentrations in plasma and serum. Clin. Chem. 22;1909, 1976. Weber, H.P., R.W. Gray, J.H. Dominguez and J. Lemann, Jr. The lack of effect of chronic metabolic acidosis on 25-OH-vitamin D metabolism and serum parathyroid hormone in humans. J. Clin. & Metab. 43:1047, 1976.